[Frontiers in Bioscience 14, 689-698, January 1, 2009]

Vascular changes after cardiac surgery: role of NOS, COX, kinases, and growth factors

Neel R. Sodha, Richard T. Clements, Frank W. Sellke

Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215

FIGURES

Figure 1. Alterations in vascular NOS and COX signaling pathways following cardiac surgery. A) NOS and COX signaling under normal conditions and B) following cardiac surgery Red arrows indicate relative changes following cardiac surgery. Blue arrows depict eNOS associated signaling alterations, green arrows represent iNOS dependent signaling alterations. Abbreviations used: EC - endothelial Cells; VSMC - vascular smooth muscle cells; COX - cyclooxygenase; eNOS - endothelial nitric oxide synthase; iNOS - inducible nitric oxide synthase; RNS/ROS - reactive oxygen/nitrogen species, NO - nitric oxide - sGC - soluble Guanylate Cyclase; cGMP - cyclic Guanosine Monophosphate TXA2 - thromboxane A2; PGF2-alpha- prostaglandin F2-alpha ; PGI2 - prostacyclin; PGE2 - prostaglandin E2.

Figure 2. Alterations in (A) catecholamine signaling and (B) inflammatory mediators following cardiac surgery. A) Red arrows indicate relative changes shown to be increased following cardiac surgery. Dotted arrows represent effects associated with sustained catecholamine exposure. Early during reperfusion increased catecholamines promote smooth muscle contraction through increased activation of components of adrenergic signaling. Sustained catecholamine exposure results in down regulation of receptor signaling and impaired perfusion. B) Numerous inflammatory mediators from white cells subjected to CPB can produce increased production of inflammatory mediators from the target vascular tissues. Abbreviations: NE - norepinephrine; Epi - Epinephrine; a1-AR - alpha 1 adrenergic receptor; PLC - phospholipase C; PIP2 - phosphatidyl inositol 4,5 bisphosphate; IP3 - inositol tri-phosphate; DAG - Diacylglycerol; PKC - protein kinase C; MLCK - myosin light chain kinase; ERK - extracellular signal regulated kinase; p38-MAPK - p38 mitogen activated protein kinase, TNF - tumor necrosis factor; IL - interleukin.